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Otto C. Boerman

Bio: Otto C. Boerman is an academic researcher from Radboud University Nijmegen. The author has contributed to research in topics: Radioimmunotherapy & In vivo. The author has an hindex of 66, co-authored 355 publications receiving 15882 citations. Previous affiliations of Otto C. Boerman include Radboud University Nijmegen Medical Centre.


Papers
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Journal ArticleDOI
TL;DR: In vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information and appears clinically safe and well suited to monitor cellular therapy in humans.
Abstract: The success of cellular therapies will depend in part on accurate delivery of cells to target organs. In dendritic cell therapy, in particular, delivery and subsequent migration of cells to regional lymph nodes is essential for effective stimulation of the immune system. We show here that in vivo magnetic resonance tracking of magnetically labeled cells is feasible in humans for detecting very low numbers of dendritic cells in conjunction with detailed anatomical information. Autologous dendritic cells were labeled with a clinical superparamagnetic iron oxide formulation or (111)In-oxine and were co-injected intranodally in melanoma patients under ultrasound guidance. In contrast to scintigraphic imaging, magnetic resonance imaging (MRI) allowed assessment of the accuracy of dendritic cell delivery and of inter- and intra-nodal cell migration patterns. MRI cell tracking using iron oxides appears clinically safe and well suited to monitor cellular therapy in humans.

797 citations

Journal Article
TL;DR: It is demonstrated that in vitro-generated mature, but not immature dendritic cells, efficiently migrate into the T-cell areas of lymph nodes of melanoma patients.
Abstract: Dendritic cells are the professional antigen-presenting cells of the immune system. To induce an effective immune response, these cells should not only express high levels of MHC and costimulatory molecules but also migrate into the lymph nodes to interact with naive T cells. Here, we demonstrate that in vitro-generated mature, but not immature dendritic cells, efficiently migrate into the T-cell areas of lymph nodes of melanoma patients. This difference is confirmed by in vitro studies, in which immature dendritic cells are strongly adherent, whereas mature dendritic cells remain highly motile. Our present findings demonstrate that the ability of dendritic cells to mount a proper immune response correlates with their ability to migrate both in vitro and in vivo.

515 citations

Journal Article
TL;DR: Administration of sterically stabilized PEG liposomes significantly altered the pharmacokinetic behavior of subsequently injected PEGliposomes in a time- and frequency-dependent manner, and the observed phenomenon may have important implications for the repeated administration of sterially stabilized liposome for targeted drug delivery.
Abstract: Sterically stabilized liposomes are considered promising carriers of therapeutic agents because they can facilitate controlled release of the drugs, thereby reducing drug-related toxicity and/or targeted delivery of drugs. Herein, we studied the pharmacokinetics and biodistribution of repeated injections of radiolabeled polyethyleneglycol (PEG) liposomes. Weekly injections of 99m Tc-PEG liposomes dramatically influenced the circulatory half-life in rats. Biodistribution 4 h after the second dose showed a significantly reduced blood content (from 52.6 ± 3.7 to 0.6 ± 0.1% injected dose (ID), P P P

477 citations

Journal ArticleDOI
TL;DR: Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.
Abstract: OBJECTIVE: To review the literature with regard to the incidence and prognostic significance of peritoneal seeding during surgery for primary colorectal cancer (CRC), the incidence of intraperitoneal recurrence of CRC, and the current treatment strategies of established PC of colorectal origin, with special focus on cytoreductive surgery and intraperitoneal chemotherapy (IPEC). SUMMARY BACKGROUND DATA: Although hematogenous dissemination forms the greatest threat to patients with CRC, peritoneal carcinomatosis (PC), presumably arising from intraperitoneal seeding of cancer cells, is a relatively frequent event in patients with recurrent CRC. METHODS: The PubMed and Medline literature databases were searched for pertinent publications regarding the incidence and prognostic significance of exfoliated tumor cells in the peritoneal cavity during curative surgery for primary CRC, the incidence of intraperitoneal recurrence of CRC, and the therapeutic results of systemic chemotherapy or cytoreductive surgery followed by IPEC. RESULTS: The incidence of peritoneal seeding during potentially curative surgery for primary CRC, as reported in 12 patient series, varied widely, from 3% to 28%, which may be explained by differences in methods to detect tumor cells. PC is encountered in approximately 7% of patients at primary surgery, in approximately 4% to 19% of patients during follow-up after curative surgery, in up to 44% of patients with recurrent CRC who require relaparotomy, and in 40% to 80% of patients who succumb to CRC. The reported median survival after systemic 5-fluorouracil-based chemotherapy for PC varies from 5.2 to 12.6 months. Median survival after aggressive cytoreductive surgery followed by (hyperthermic) IPEC in selected patients, as reported in 16 patient series, tends to be better and varies from 12 to 32 months at the cost of morbidity and mortality rates of 14% to 55% and 0% to 19%, respectively. One randomized controlled trial has been published confirming the superiority of aggressive surgical cytoreduction and intraperitoneal chemotherapy over strictly palliative treatment. CONCLUSIONS: Peritoneal seeding of cancer cells possibly leading to PC is a rather common phenomenon in patients with CRC. Cytoreductive surgery and adjuvant (hyperthermic) IPEC have been shown to be efficacious in selected patients and should therefore be considered in patients with resectable PC of colorectal origin.

471 citations

Journal ArticleDOI
TL;DR: The ability to bind highly stable Al18F to metal-binding ligands is a promising new labeling method that should be applicable to a diverse array of molecules for PET.
Abstract: Small biomolecules are typically radiolabeled with 18F by binding it to a carbon atom, a process that usually is designed uniquely for each new molecule and requires several steps and hours to produce. We report a facile method wherein 18F is first attached to aluminum as Al18F, which is then bound to a chelate attached to a peptide, forming a stable Al18F-chelate-peptide complex in an efficient 1-pot process. Methods: For proof of principle, this method was applied to a peptide suitable for use in a bispecific antibody pretargeting method. A solution of AlCl3·6H2O in a pH 4.0 sodium-acetate buffer was mixed with an aqueous solution of 18F to form the Al18F complex. This was added to a solution of IMP 449 (NOTA-p-Bn-CS-d-Ala-d-Lys(HSG)-d-Tyr-d-Lys(HSG)-NH2) (NOTA-p-Bn-CS is made from S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid; HSG is histamine-succinyl-glycine) and heated to 100°C for 15 min. In vitro and in vivo stability and targeting ability of the Al18F-IMP 449 were examined in nude mice bearing LS174T human colonic tumors pretargeted with an anti-CEACAM5 bispecific antibody (TF2). Results: The radiolabeled peptide was produced in 5%−20% yield with an estimated specific activity of 18,500–48,100 GBq (500–1,300 Ci)/mmol. The Al18F-IMP 449 was stable for 4 h in serum in vitro, and in animals, activity isolated in the urine 30 min after injection was bound to the peptide. Nonchelated Al18F had higher tissue uptake, particularly in the bones, than the chelated Al18F-IMP 449, which cleared rapidly from the body by urinary excretion. Tumor uptake was 30-fold higher with TF2-pretargeted Al18F-IMP 449 than with the peptide alone. Dynamic PET showed tumor localization within 30 min and rapid and thorough clearance from the body. Conclusion: The ability to bind highly stable Al18F to metal-binding ligands is a promising new labeling method that should be applicable to a diverse array of molecules for PET.

347 citations


Cited by
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TL;DR: It is reported that magnetite nanoparticles in fact possess an intrinsic enzyme mimetic activity similar to that found in natural peroxidases, which are widely used to oxidize organic substrates in the treatment of wastewater or as detection tools.
Abstract: Nanoparticles containing magnetic materials, such as magnetite (Fe3O4), are particularly useful for imaging and separation techniques. As these nanoparticles are generally considered to be biologically and chemically inert, they are typically coated with metal catalysts, antibodies or enzymes to increase their functionality as separation agents. Here, we report that magnetite nanoparticles in fact possess an intrinsic enzyme mimetic activity similar to that found in natural peroxidases, which are widely used to oxidize organic substrates in the treatment of wastewater or as detection tools. Based on this finding, we have developed a novel immunoassay in which antibody-modified magnetite nanoparticles provide three functions: capture, separation and detection. The stability, ease of production and versatility of these nanoparticles makes them a powerful tool for a wide range of potential applications in medicine, biotechnology and environmental chemistry.

4,500 citations

Journal Article
TL;DR: The surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition, are explored and the rational approaches in the design as well as the biological performance of such constructs are assessed.
Abstract: The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

3,413 citations

Journal ArticleDOI
TL;DR: Clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.
Abstract: The integrin family of cell adhesion receptors regulates a diverse array of cellular functions crucial to the initiation, progression and metastasis of solid tumours. The importance of integrins in several cell types that affect tumour progression has made them an appealing target for cancer therapy. Integrin antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide, have shown encouraging activity in Phase II clinical trials and cilengitide is currently being tested in a Phase III trial in patients with glioblastoma. These exciting clinical developments emphasize the need to identify how integrin antagonists influence the tumour and its microenvironment.

2,894 citations

Journal ArticleDOI
TL;DR: PEG is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery and alternative polymers will be evaluated.
Abstract: Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.

2,815 citations